[No authors listed]
Polypeptide Nâacetylgalactosaminyltransferase 6 (GALNT6), which is involved in the initiation of Oâglycosylation, has been reported to play crucial roles in mammary carcinogenesis through binding to several substrates; however, its biological roles in mediating growthâpromoting effects remain unknown. The present study demonstrated a crucial pathophysiological role of GALNT6 through its Oâglycosylation of lectin galactosideâbinding soluble 3 binding protein (LGALS3BP), a secreted growthâpromoting glycoprotein, in breast cancer growth. The Cancer Genome Atlas data analysis revealed that high expression levels of GALNT6 were significantly associated with poor prognosis of breast cancer. GALNT6 Oâglycosylated LGALS3BP in breast cancer cells, whereas knockdown of GALNT6 by siRNA led to the inhibition of both the Oâglycosylation and secretion of LGALS3BP, resulting in the suppression of breast cancer cell growth. Notably, LGALS3BP is potentially Oâglycosylated at three sites (T556, T571 and S582) by GALNT6, thereby promoting autocrine cell growth, whereas the expression of LGALS3BP with three Ala substitutions (T556A, T571A and S582A) in cells drastically reduced GALNT6âdependent LGALS3BP Oâglycosylation and secretion, resulting in suppression of autocrine growthâpromoting effect. The findings of the present study suggest that the GALNT6âLGALS3BP axis is crucial for breast cancer cell proliferation and may be a therapeutic target and biomarker for mammary tumors.
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